biostudies-literatureMedina-Gutierrez EInstituto de Salud Carlos III (Spain)Josep Carreras Leukaemia Research InstituteAGAUR (Spain)CIBER-BBN (Spain)Agencia Estatal de Investigación (AEI, Spain) and Fondo Europeo de Desarrollo Regional (FEDER, European Union)Instituto de Salud Carlos IIIAgency for Administration of University and ResearchJosep Carreras Leukemia Research Institute (Spain)Biomedical Research Networking Center in Bioengineering, Biomaterials and Nanomedicine85https://www.ebi.ac.uk/biostudies/studies/S-EPMC9818013biostudies-literatureUnknown15(1)Patients with advanced endometrial cancer (EC) show poor outcomes. Thus, the development of new therapeutic approaches to prevent metastasis development in high-risk patients is an unmet need. CXCR4 is overexpressed in EC tumor tissue, epitomizing an unexploited therapeutic target for this malignancy. The in vitro antitumor activity of two CXCR4-targeted nanoparticles, including either the <i>C. diphtheriae</i> (T22-DITOX-H6) or <i>P. aeruginosa</i> (T22-PE24-H6) toxin, was evaluated using viability assays. Apoptotic activation was assessed by DAPI and caspase-3 and PARP cleavage in cell blocks. Both nanotoxins were repeatedly administrated to a subcutaneous EC mouse model, whereas T22-DITOX-H6 was also used in a highly metastatic EC orthotopic model. Tumor burden was assessed through biolCancersPotent Anticancer Activity of CXCR4-Targeted Nanostructured Toxins in Aggressive Endometrial Cancer Models.PMC9818013grant BIO2016-76063-R, AEI/FEDER, UE to Antonio Villaverde and grant PID2019-105416RBI00/AEI/10.13039/501100011033 to Esther VázquezPI21/00159, PI18/00650 and EU COST Action CA 17140 to Ramon Mangues and PI20/00400 to Ugutz UnzuetaPID2019-105416RBI00/AEI/10.13039/5011000110332017-SGR-865BIO2016-76063-RPI21/00159P/AG to Ramon Mangues2017SGR-229CB06/01/1031PI20/00400CB06/01/1031 and 4NanoMets to Ramon Mangues, VENOM4CANCER to Antonio Villaverde, NANOREMOTE to Esther Vázquez and NANOSCAPE to Ugutz UnzuetaCP19/00028PI18/006502017-SGR-865 to Ramon Mangues, and 2017SGR-229 to Antonio VillaverdeMangues RAlamo PAlba-Castellon LVillaverde ACasanova IMedina-Gutierrez EVazquez EGarcia-Leon AUnzueta UGallardo AfalsePotent Anticancer Activity of CXCR4-Targeted Nanostructured Toxins in Aggressive Endometrial Cancer Models.Patients with advanced endometrial cancer (EC) show poor outcomes. Thus, the development of new therapeutic approaches to prevent metastasis development in high-risk patients is an unmet need. CXCR4 is overexpressed in EC tumor tissue, epitomizing an unexploited therapeutic target for this malignancy. The in vitro antitumor activity of two CXCR4-targeted nanoparticles, including either the <i>C. diphtheriae</i> (T22-DITOX-H6) or <i>P. aeruginosa</i> (T22-PE24-H6) toxin, was evaluated using viability assays. Apoptotic activation was assessed by DAPI and caspase-3 and PARP cleavage in cell blocks. Both nanotoxins were repeatedly administrated to a subcutaneous EC mouse model, whereas T22-DITOX-H6 was also used in a highly metastatic EC orthotopic model. Tumor burden was assessed through biol2022-01-01T00:00:00Z2022 Dec2026-06-21T03:21:10.552Z2025-04-04T20:33:16.675ZS-EPMC98180133661208110.3390/cancers15010085